Acute otitis media (AOM) is defined by the presence of middle ear effusion (MEE) with acute onset of symptoms of inflammation of the middle ear. Although more than half of patients who develop AOM have fever (Chandler, et al. 2007. Consistency of diagnostic criteria for acute otitis media: a review of the recent literature. Clin. Pediatr. (Phila.) 46:99-108), the condition is considered a localized, mucosal infection. Currently, AOM is regarded as relatively benign due to spontaneous resolution of the infection in a majority of patients (Rosenfeld, R. M., and D. Kay. 2003. Natural history of untreated otitis media. Laryngoscope 113:1645-1657.). The complications and sequelae of bacterial systemic invasion from the middle ear, including mastoiditis, brain abscess, and meningitis, are sufficiently rare that they have recently been considered less consequential in comparison to the consequences from the costs of antimicrobial treatment and overtreatment (American Academy of Pediatrics. 2004. Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media. Pediatrics 113:1451-1465).
The cause and pathogenesis of otitis media are multifactorial, involving viral and bacterial infections. The most frequently isolated bacteria in AOM are Spn (20 to 55% of cases), nontypeable Haemophilus influenzae (NTHi) (15 to 40%), and Moraxella catarrhalis (Mcat) (10 to 25%) (Casey, J. R., D. G. Adlowitz, and M. E. Pichichero. 2010. New patterns in the otopathogens causing acute otitis media six to eight years after introduction of pneumococcal conjugate vaccine. Pediatr. Infect. Dis. J. 29:304-309., Howie, V. M., R. Dillard, and B. Lawrence. 1985. In vivo sensitivity test in otitis media: efficacy of antibiotics. Pediatrics 75:8-13, Klein, J. O. 1994. Otitis media. Clin. Infect. Dis. 19:823-833). When bacteria gain entry into the middle ear space, they damage the middle ear mucosa directly by releasing toxins and indirectly by provoking both specific immunological and general inflammatory responses in the host. A prominent feature of the host response is an influx of inflammatory cells into the middle ear.
Due to difficulty in diagnosing AOM unnecessary antibiotic treatment is common which can lead to antibiotic resistant pathogens. Prevalence of antibiotic resistant pathogens in the upper respiratory tract has increased (McCracken G H J. Emergence of resistant Streptococcus pneumoniae: a problem in pediatrics. Pediatr Infect Dis J 1995; 14: 424-428). The increase in antibiotic resistant pathogens provides potential hazards associated with the future treatment of bacterial infections. New diagnostic tools to distinguish AOM from normal variants of eardrum appearance during a viral upper respiratory tract infection could counteract this development, since AOM diagnosis often results in the prescription of antibiotics.
Not only is an accurate diagnosis beneficial to avoid excessive and unnecessary antibiotic prescriptions, but a quick and efficient manner of determining if resolution of AOM occurs after treatment or observation, especially in children, is needed. The eardrum often does not return to its normal appearance in some patients for 6-12 weeks after infection. Concerned that AOM persists in such cases, many clinicians re-treat with even broader spectrum antibiotics when a follow up examination is not completely normal. Thus, another useful tool for AOM management would be a test that can be used to monitor individuals for the presence of infection after treatment.
The present methods, compositions, and kits provide a diagnostic tool based on specific biomarkers, such as S100A12, IL-10 and ICAM-1, samples, such as in serum, to determine whether AOM is present and caused by a bacterial infection and in follow up to determine if the infection has resolved. The biomarkers can be used in combination or alone.